PPl 15: The First Brown Dwarf Spectroscopic Binary

PPl 15 is the first object to have been confirmed as a brown dwarf by the lithium test (in 1995), though its inferred mass was very close to the substellar limit. It is a member of the Pleiades open cluster. Its position in a cluster color-magnitude diagram suggested that it might be binary, and preliminary indications that it is a double-lined spectroscopic binary were reported by us in 1997. Here we report on the results of a consecutive week of Keck HIRES observations of this system, which yield its orbit. It has a period of about 5.8 days, and an eccentricity of 0.4+/-0.05. The rotation of the stars is slow for this class of objects. Because the system luminosity is divided between 2 objects with a mass ratio of 0.85, this renders each of them an incontrovertible brown dwarf, with masses between 60-70 jupiters. We show that component B is a little redder than A by studying their wavelength-dependent line ratios, and that this variation is compatible with the mass ratio. We confirm that the system has lithium, but cannot support the original conclusion that it is depleted (which would be surprising, given the new masses). This is a system of very close objects which, if they had combined, would have produced a low mass star. We discuss the implications of this discovery for the theories of binary formation and formation of very low mass objects.Comment: Latex, 18 pages, 4 figures, submitted to Astron.

SMURFLite: combining simplified Markov random fields with simulated evolution improves remote homology detection for beta-structural proteins into the twilight zone

Motivation: One of the most successful methods to date for recognizing protein sequences that are evolutionarily related has been profile hidden Markov models (HMMs). However, these models do not capture pairwise statistical preferences of residues that are hydrogen bonded in beta sheets. These dependencies have been partially captured in the HMM setting by simulated evolution in the training phase and can be fully captured by Markov random fields (MRFs). However, the MRFs can be computationally prohibitive when beta strands are interleaved in complex topologies. We introduce SMURFLite, a method that combines both simplified MRFs and simulated evolution to substantially improve remote homology detection for beta structures. Unlike previous MRF-based methods, SMURFLite is computationally feasible on any beta-structural motif

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

The Lantern Vol. 29, No. 2, Spring 1962

• A Deadly Diatribe on Daydreaming • Iter Animae • In Retrospection • Collegiate, Collegiate, Yes We Are Collegiate • Saint Zachary • Lost Horizons • Rune Green Stones • Druidics • Leanthalamion • Thoughts on Leaving Derr Hall • Opus 36; Literature 3 • Chinese Gill • Times of Sandhttps://digitalcommons.ursinus.edu/lantern/1082/thumbnail.jp

Expression of hypoxia-inducible factor 1α in thyroid carcinomas

Hypoxia-inducible factor 1α (HIF-1α) is upregulated by hypoxia and oncogenic signalling in many solid tumours. Its regulation and function in thyroid carcinomas are unknown. We evaluated the regulation of HIF-1α and target gene expression in primary thyroid carcinomas and thyroid carcinoma cell lines (BcPAP, WRO, FTC-133 and 8505c). HIF-1α was not detectable in normal tissue but was expressed in thyroid carcinomas. Dedifferentiated anaplastic tumours (ATCs) exhibited high levels of nuclear HIF-1α staining. The HIF-1 target glucose transporter 1 was expressed to a similar level in all tumour types, whereas carbonic anhydrase-9 was significantly elevated in ATCs. In vitro studies revealed a functionally active HIF-1α pathway in thyroid cells with transcriptional activation observed after graded hypoxia (1% O2, anoxia) or treatment with a hypoxia mimetic cobalt chloride. High basal and hypoxia-induced expression of HIF-1α in FTC-133 cells that harbour a phosphatase and tensin homologue (PTEN) mutation was reduced by introduction of wild-type PTEN. Similarly, pharmacological inhibition of the phosphoinositide 3-kinase (PI3K) pathway using LY294002 inhibited HIF-1α and HIF-1α targets in all cell lines, including those with B-RAF mutations (BcPAP and 8505c). In contrast, the effects of inhibition of the RAF/MEK/extracellular signal-regulated kinase pathway were restricted by environmental condition and B-RAF mutation status. HIF-1 is functionally expressed in thyroid carcinomas and is regulated not only by hypoxia but also via growth factor signalling pathways and, in particular, the PI3K pathway. Given the strong association of HIF-1α with an aggressive disease phenotype and therapeutic resistance, this pathway may be an attractive target for improved therapy in thyroid carcinomas

Wound-on-tension for two drum winders

The two drum winder remains to be a high productivity winder for rewinding some paper and nonwoven webs at very high speeds. Winding models of varied capabilities exist for center winders, center winders with rider rollers, and surface winders. Winding models for two drum winders however are still in the introductory stages. Two drum winders are somewhat more complex than other winders due to the number of rollers, driven and undriven, which impinge the surface of the winding roll. The objectives of this paper are to show the influence of various winder operating parameters and thread path on the wound-on-tension in the outer layer (WOT).Mechanical and Aerospace Engineerin

The Schr\"oder functional equation and its relation to the invariant measures of chaotic maps

The aim of this paper is to show that the invariant measure for a class of one dimensional chaotic maps, $T(x)$, is an extended solution of the Schr\"oder functional equation, $q(T(x))=\lambda q(x)$, induced by them. Hence, we give an unified treatment of a collection of exactly solved examples worked out in the current literature. In particular, we show that these examples belongs to a class of functions introduced by Mira, (see text). Moreover, as a new example, we compute the invariant densities for a class of rational maps having the Weierstrass $\wp$ functions as an invariant one. Also, we study the relation between that equation and the well known Frobenius-Perron and Koopman's operators.Comment: 9 page

The Lantern Vol. 30, No. 1, February 1963

• Mechanical Duplicity • The Practical Profits of Purism • \u27Tis Better • Misha • Manuel • An American Fairy Tale • The Christ of Christopher Street • Nocturne • Various Reflections • He Came and Gently Lifted Me • Poem, In a Minor Key • World Fell to Ruin • The Map • On Being Jilted • Manna • Traitor • The Leaves Cling • Oh Freedom! • The Insurance Man • Translation - The Vampire • Four Poems • Sanguis • Phoney is the Color of My Love\u27s Life • To a Barmaidhttps://digitalcommons.ursinus.edu/lantern/1083/thumbnail.jp

The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation

We thank Cowen lab members for helpful discussions. We also thank David Rogers (University of Tennessee) for sharing microarray analysis of the CAS5 homozygous mutant, and Li Ang (University of Macau) for assistance in optimizing the ChIP-Seq experiments. J.L.X. is supported by a Canadian Institutes of Health Research Doctoral award and M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072). B.T.G. holds an Ontario Graduate Scholarship. C.B. and B.J.A. are supported by the Canadian Institutes of Health Research Foundation Grants (FDN-143264 and -143265). D.J.K. is supported by a National Institute of Allergy and Infectious Diseases grant (1R01AI098450) and J.D.L.C.D. is supported by the University of Rochester School of Dentistry and Medicine PREP program (R25 GM064133). A.S. is supported by the Creighton University and the Nebraska Department of Health and Human Services (LB506-2017-55). K.H.W. is supported by the Science and Technology Development Fund of Macau S.A.R. (FDCT; 085/2014/A2). L.E.C. is supported by the Canadian Institutes of Health Research Operating Grants (MOP-86452 and MOP-119520), the Natural Sciences and Engineering Council (NSERC) of Canada Discovery Grants (06261 and 462167), and an NSERC E.W.R. Steacie Memorial Fellowship (477598).Peer reviewedPublisher PD